Acetyl-L-carnitine for the prevention of taxane-induced neuropathy in patients with breast cancer: a systematic review and meta-analysis

Mahnaz Momenzadeh , Amir Aria, Keyvan Ghadimi, Azadeh Moghaddas


Background and purpose: Peripheral neuropathy is one of the most prevalent and undesirable side effects of taxane-containing chemotherapy regimens. This study aimed to investigate the effect of acetyl-L-carnitine (ALC) on the prevention of taxane-induced neuropathy (TIN).

Experimental approach: MEDLINE, PubMed, Cochrane Library, Embase, Web of Science, and Google scholar were systemically applied as electronic databases from 2010 to 2019. The current systematic review was carried out based on the main considerations of PRISMA preferential reporting items for systematic review and meta-analyses. Since there was no significant discrepancy, the random-effect model was used for 12-24 weeks’ analysis (I2 = 0%, P = 0.999).

Findings/Results: Twelve related titles and abstracts were found during the search, 6 of them were excluded in the first phase. In the second phase, the full text of the remaining 6 articles was comprehensively evaluated and 3 papers were rejected. Finally, 3 articles complied with the inclusion criteria and pooled analyses. The meta-analysis showed a risk ratio of 0.796 (95% CI between 0.486 and 1.303), so, the effects model was used for 12-24 weeks’ analysis (I2 = 0%, P = 0.999) since no significant discrepancies were observed. There was no evidence of ALC’s positive effect on the prevention of TIN during 12 weeks, and it was revealed that ALC significantly increased TIN in 24 weeks.

Conclusion and implications: According to our findings, the hypothesis that ALC had a positive effect on preventing TIN in 12 weeks has not been proved; however, ALC led to an increase in the TIN in 24 weeks.


Acetyl-L-carnitine; Breast cancer; Chemotherapy; Neuropathy; Taxane.

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Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21(6):976-983. DOI: 10.1200/JCO.2003.02.063.

Sahranavard S, Khoramjouy M, Khakpash M, Askari SA, Faizi M, Mosaddegh M. Hydroethanolic extract of Lavandula angustifolia ameliorates vincristine-induced peripheral neuropathy in rats. Res Pharm Sci. 2022;17(3):265-273. DOI: 10.4103/1735-5362.343080.

Xue B, Zhao J, Fan Y, Chen S, Li W, Chen J, et al. Synthesis of taxol and docetaxel by using 10-deacetyl-7-xylosyltaxanes. Chem Biodivers. 2020;17(2):e1900631,1-7. DOI: 10.1002/cbdv.201900631.

Zhi WI, Chen P, Kwon A, Chen C, Harte SE, Piulson L, et al. Chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors: a comparison of patient-reported outcomes and quantitative sensory testing. Breast Cancer Res Treat. 2019;178(3):587-595. DOI: 10.1007/s10549-019-05416-4.

Hershman DL, Weimer LH, Wang A, Kranwinkel G, Brafman L, Fuentes D, et al. Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat. 2011;125(3):767-774. DOI: 10.1007/s10549-010-1278-0.

Cioroiu C, Weimer LH. Update on chemotherapy-induced peripheral neuropathy. Curr Neurol Neurosci Rep. 2017;17(6):47,1-8.

DOI: 10.1007/s11910-017-0757-7.

Simon NB, Danso MA, Alberico TA, Basch E, Bennett AV. The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice. Qual Life Res. 2017;26(10):2763-2772. DOI: 10.1007/s11136-017-1635-0.

Chen H, Chan YL, Linnane C, Mao Y, Anwer AG, Sapkota A, et al. L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury. Sci Rep. 2018;8(1):11201,1-16. DOI: 10.1038/s41598-018-29430-6.

Kelly GS. L-Carnitine: therapeutic applications of a conditionally-essential amino acid. Altern Med Rev. 1998;3(5):345-360. PMID: 9804680.

Pisano C, Pratesi G, Laccabue D, Zunino F, Lo Giudice P, Bellucci A, et al. Paclitaxel and cisplatin-induced neurotoxicity: a protective role of acetyl-L-carnitine. Clin Cancer Res. 2003;9(15):5756-5767.PMID: 14654561.

Sergi G, Pizzato S, Piovesan F, Trevisan C, Veronese N, Manzato E. Effects of acetyl-L-carnitine in diabetic neuropathy and other geriatric disorders. Aging Clin Exp Res. 2018;30(2):133-138. DOI: 10.1007/s40520-017-0770-3.

Di Giulio AM, Gorio A, Bertelli A, Mantegazza P, Ferraris L, Ramacci MT. Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals. Int J Clin Pharmacol Res. 1992;12(5-6):243-246. PMID: 1284499.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71,1-9. DOI: 10.1136/bmj.n71.

Panic N, Leoncini E, de Belvis G, Ricciardi W, Boccia S. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS One. 2013;8(12):e83138,1-7. DOI: 10.1371/journal.pone.0083138.

Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13(Suppl 1):S31-S34. DOI: 10.4103/sja.SJA_543_18.

Hajibandeh S, Hajibandeh S, Antoniou GA, Green PA, Maden M, Torella F. Reporting and methodological quality of randomised controlled trials in vascular and endovascular surgery. Eur J Vasc Endovasc Surg. 2015;50(5):664-670. DOI: 10.1016/j.ejvs.2015.06.114.

Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, et al. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol. 2013;31(20):2627-2633. DOI: 10.1200/JCO.2012.44.8738.

Hershman DL, Unger JM, Crew KD, Till C, Greenlee H, Minasian LM, et al. Two-year trends of taxane-induced neuropathy in women enrolled in a randomized trial of acetyl-l-carnitine (SWOG S0715). J Natl Cancer Inst. 2018;110(6):669-676. DOI: 10.1093/jnci/djx259.

Esfahani M, Sahafi S, Derakhshandeh A, Moghaddas A. The anti-wasting effects of L-carnitine supplementation on cancer: experimental data and clinical studies. Asia Pac J Clin Nutr. 2018;27(3):503-511. DOI: 10.6133/apjcn.042017.10.

Nejati M, Abbasi S, Farsaei S, Shafiee F. L-carnitine supplementation ameliorates insulin resistance in critically ill acute stroke patients: a randomized, double-blinded, placebo-controlled clinical trial. Res Pharm Sci. 2021;17(1):66-77. DOI: 10.4103/1735-5362.329927.

Jafari A, Khatami MR, Dashti-Khavidaki S, Lessan-Pezeshki M, Abdollahi A, Moghaddas A. Protective effects of l-carnitine against delayed graft function in kidney transplant recipients: a pilot, randomized, double-blinded, placebo-controlled clinical trial. J Ren Nutr. 2017;27(2):113-126. DOI: 10.1053/j.jrn.2016.11.002.

Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk. Breast Cancer Res Treat. 2016;159(2):327-333. DOI: 10.1007/s10549-016-3939-0.

Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV. Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population-based PROFILES registry. J Clin Oncol. 2013;31(21):2699-2707. DOI: 10.1200/JCO.2013.49.1514.

Ezendam NP, Pijlman B, Bhugwandass C, Pruijt JF, Mols F, Vos MC, et al. Chemotherapy-induced peripheral neuropathy and its impact on health-related quality of life among ovarian cancer survivors: results from the population-based PROFILES registry. Gynecol Oncol. 2014;135(3):510-517. DOI: 10.1016/j.ygyno.2014.09.016.

Winters-Stone KM, Horak F, Jacobs PG, Trubowitz P, Dieckmann NF, Stoyles S, et al. Falls, functioning, and disability among women with persistent symptoms of chemotherapy-induced peripheral neuropathy. J Clin Oncol. 2017;35(23): 2604-2612. DOI: 10.1200/JCO.2016.71.3552.

Pereira S, Fontes F, Sonin T, Dias T, Fragoso M, Castro-Lopes JM, et al. Chemotherapy-induced peripheral neuropathy after neoadjuvant or adjuvant treatment of breast cancer: a prospective cohort study. Support Care Cancer. 2016;24(4):1571-1581. DOI: 10.1007/s00520-015-2935-y.

Xiao WH, Zheng H, Bennett GJ. Characterization of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel. Neuroscience. 2012;203:194-206. DOI: 10.1016/j.neuroscience.2011.12.023.

Zheng H, Xiao WH, Bennett GJ. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy. Exp Neurol. 2011;232(2):154-161.DOI: 10.1016/j.expneurol.2011.08.016.

Xiao W, Naso L, Bennett GJ. Experimental studies of potential analgesics for the treatment of chemotherapy-evoked painful peripheral neuropathies. Pain Med. 2008;9(5):505-517. DOI: 10.1111/j.1526-4637.2007.00301.x.

Malaguarnera M, Risino C, Gargante MP, Oreste G, Barone G, Tomasello AV, et al. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia. World J Gastroenterol. 2006;12(28):4541-4545. DOI: 10.3748/wjg.v12.i28.4541.

van Dam DG, Beijers AJ, Vreugdenhil G. Acetyl-L-carnitine undervalued in the treatment of chemotherapy-induced peripheral neuropathy? Acta Oncol. 2016;55(12):1495-1497. DOI: 10.1080/0284186X.2016.1220678.

Leen AJ, Yap DWT, Teo CB, Tan BKJ, Molassiotis A, Ishiguro H, et al. A systematic review and meta-analysis of the effectiveness of neuroprotectants for paclitaxel-induced peripheral neuropathy. Front Oncol. 2022;11:763229,1-15. DOI: 10.3389/fonc.2021.763229.


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